tbuckley/cabot-search huggingface dataset:
Transcolonic lumen-apposing metal stent placement complicating a palliative endoscopic ultrasound-guided gastrojejunostomy
Authors: Viliam Masaryk, Frank Meyer, Uwe Will
Journal: Endoscopy (2023)

A rare complication associated with an endoscopic ultrasound (EUS)-guided gastroenteroanastomosis (EUS-GE) [1] created using a lumen-apposing metal stent (LAMS) is stent dislocation into the colon with a resulting gastrocolostomy [2] [3] [4]. We report an EUS-GE with stent dislocation and formation of a gastrocolostomy and a colojejunal fistula that was rescued by transcolonic insertion of an intestinal stent ([Video 1]).
A novel peroral pancreatoscopy combined endoscopic ultrasonography-assisted rendezvous procedure: a new strategy for bridging disconnected pancreatic duct syndrome
Authors: Peng Wang, Tao Yu, Hongbo Ren, Rui Ji, Zhen Li, Guangchao Li, Ning Zhong
Journal: Endoscopy (2023)

A 48-year-old man with a history of acute necrotizing pancreatitis presented to our institution for management of a persistent external pancreatic fistula. He had required percutaneous catheter drainage for a pseudocyst in the pancreatic neck before this complication. A pancreatogram showed that the pseudocyst was in communication with the main pancreatic duct (MPD) in the head; however, there was no opacification of the upstream MPD, confirming complete MPD disconnection ([Fig. 1]). It had not been possible to traverse the MPD disconnection with a guidewire during prior attempts.
Endoscopic ultrasound-guided transgastric pyogenic liver abscess drainage using a drill dilator
Authors: Takeshi Ogura, Yuki Uba, Mitsuki Tomita, Masahiro Yamamura, Hiroki Nishikawa
Journal: Endoscopy (2023)

Percutaneous transhepatic drainage (PTD) is the gold standard treatment for pyogenic liver abscess [1], but PTD can be challenging where a pyogenic liver abscess is located at a site that is difficult to access via the percutaneous approach and in patients with severe dementia, in whom self-removal of the tube is a risk. An endoscopic ultrasound (EUS)-guided procedure offers internal drainage via a transluminal approach and may be an alternative option in such cases. Several studies have reported the clinical benefits of EUS-guided access for pyogenic liver abscesses [2] [3] [4]; however, this technique requires tract dilation prior to metal stent deployment. In patients with a pyogenic liver abscess, severe inflammation can cause the cystic wall to become thickened and hardened and this can make tract dilation challenging. A novel drill dilator has recently become available in Japan (Tornus ES; Asahi Intecc) ([Fig. 1]) [5]. This allows a tract to be easily dilated using a clockwise rotation of the device handle, without force needing to be applied. We herein describe EUS-guided transgastric pyogenic liver abscess drainage using a drill dilator.
Removal of a broken percutaneous transhepatic biliary drainage catheter by cholangioscopy through a lumen-apposing metal stent used for choledochoduodenostomy
Authors: Il Sang Shin, Yeon Han Song, Jong Ho Moon, Yun Nah Lee, Jun Ho Myeong
Journal: Endoscopy (2023)

Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) using a lumen-apposing metal stent (LAMS) is an alternative procedure for biliary decompression in patients with distal malignant biliary strictures [1] [2] [3] [4]. Although this approach results in a new connecting passage into the bile duct, there are few reports of direct visualization into the bile duct through a LAMS used for CDS [5]. We present a procedure for the removal of a broken percutaneous transhepatic biliary drainage (PTBD) catheter through a LAMS used for CDS.
A novel tapered plastic stent with an ultrafine delivery system for one-step endoscopic ultrasound-guided hepaticogastrostomy
Authors: Saburo Matsubara, Keito Nakagawa, Kentaro Suda, Takeshi Otsuka, Masashi Oka, Sumiko Nagoshi
Journal: Endoscopy (2023)

A 76-year-old woman was admitted to our hospital with obstructive jaundice due to pancreas head cancer ([Fig. 1]). Endoscopic transpapillary biliary drainage was attempted but was unsuccessful owing to duodenal invasion. We therefore tried one-step endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) using a novel stent system (Crane stent; SB-Kawasumi, Kanagawa, Japan). The stent system comprises a straight-type, 7-Fr, plastic stent with a tapered tip of 4.7 Fr, an inner catheter with an extremely fine 2.5-Fr tip designed for use with a 0.025-inch guidewire, and a pusher connected to the stent allowing it to be pulled back ([Fig. 2]). A stent with a length of 15 cm between the flaps was selected.
Redo endoscopic sleeve gastroplasty
Authors: Sardar Shah-Khan, Yousaf Hadi, Mohamed Zitun, Arunkumar Krishnan, Shyam Thakkar, Shailendra Singh
Journal: Endoscopy (2023)

Endoscopic sleeve gastroplasty (ESG) has emerged as a minimally invasive treatment option for obesity. In selected patients who are unable to lose weight after ESG, redo ESG can be performed ([Video 1]).
Prefixed purse-string suture used as a new approach to resect a submucosal tumor in the ileocecal region
Authors: Xiao-jie Huang, Xiao-lu Lin, Wan-yin Deng
Journal: Endoscopy (2023)

Perforation is a significant problem that has hindered the development of endoscopic resection techniques. In 2004, Japanese endoscopists introduced the use of nylon rope and titanium clips to close the perforated wound that resulted from endoscopic mucosal resection (EMR) [1]. More recently, endoscopists have considered substituting "active perforation" for "passive perforation" for lesions where perforation is unavoidable. On this basis, we propose a new method for the endoscopic resection of submucosal tumors to avoid intra-abdominal infection and/or tumor seeding.
Cryotherapy for the treatment of benign refractory rectal bleeding
Authors: Danse Bi, Sarah Alghamdi, Olaya I. Brewer Gutierrez
Journal: Endoscopy (2023)

Endoscopic cryotherapy has been applied in the treatment of various gastrointestinal disorders [1] [2] [3]. Specifically, it has been demonstrated to be successful in the treatment of mucosal bleeding [3]. It achieves hemostasis by delivering a cryogen (liquid nitrogen, nitrous oxide, or carbon dioxide) that results in superficial mucosal freezing and thawing [2]. We describe the case of a woman with recurrent rectal bleeding in whom surgical management had failed who was treated with endoscopic cryotherapy.
Direct compression hemostasis using a balloon dilator for bleeding after esophageal stent placement
Authors: Noboru Kawata, Kazuya Hosotani, Hiroyuki Ono
Journal: Endoscopy (2023)

The European Society of Gastrointestinal Endoscopy guidelines recommend the placement of self-expandable metal stents (SEMSs) for palliation of malignant dysphagia over other treatments [1]. Although esophageal stenting enables maintenance of oral intake and improved quality of life, it carries the risk of life-threatening adverse events such as bleeding [2] [3]. Herein, we report a case in which hemostasis was achieved using an endoscopic balloon dilator for massive bleeding after esophageal SEMS placement.
Lumen-apposing metal stent placement after endoscopic ultrasound-guided duodenojejunal anastomosis for direct access to excluded jejunal limb: findings after 5 years
Authors: Francesca D’Errico, Serge Derhy, Gianfranco Donatelli
Journal: Endoscopy (2023)

Since their introduction, lumen-apposing metal stents (LAMSs) have been used successfully for symptomatic intra-abdominal collections [1] and biliary system (gallbladder, common bile duct) drainage [2]. More recently, they have also been used for gastrointestinal anastomosis [3]. We previously reported on a case series of 11 consecutive patients who underwent endoscopic ultrasound-guided duodeno- and jejunojejunal anastomosis with LAMS to obtain direct access to the excluded jejunal limb in patients with hepatico-jejunal stricture [3]. During an average follow-up of 781 days (SD 253.1 days) after duodenojejunal anastomosis, LAMSs were still in place with no evidence of adverse events. The aim of leaving the LAMS in place was to keep patent access to the hepatico-jejunostomy even after resolution of the stricture given its high recurrence rate.
Intra-abdominal haemorrhage following an endoscopic retrograde cholangiopancreatography-related procedure: a rare complication
Authors: Kayoko Kuno, Yasuki Hori, Kentaro Matsuura, Kazuki Hayashi, Itaru Naitoh, Michihiro Yoshida, Hiromi Kataoka
Journal: Endoscopy (2023)

Endoscopic retrograde cholangiopancreatography (ERCP)-related procedures are used for the treatment of various pancreaticobiliary diseases. Bleeding is a complication of ERCP-related procedures (incidence 1.34 % [1]). Most bleeding is intraluminal [1] [2], which is readily diagnosed during the procedure, but intra-abdominal hemorrhage is extremely rare and may occur as a delayed event. Herein, we report a case of intra-abdominal hemorrhage associated with an ERCP-related procedure that was successfully treated by transcatheter arterial embolisation (TAE) [3] ([Video 1]).
Cutting into the black sea: endoscopic submucosal dissection using a clip with line for a rectal polyp with severe fibrosis after tattooing
Authors: Satoki Shichijo, Takehiro Ninomiya, Tomoki Michida, Masayoshi Yasui, Yoji Takeuchi
Journal: Endoscopy (2023)

A 75-year-old woman underwent a follow-up colonoscopy after polypectomy of colorectal adenomas. A 20-mm polyp with submucosal invasion was diagnosed endoscopically in the lower rectum, marked with tattoo, and the patient was then referred to our institute for surgery.
Endoscopic ultrasound-guided hepaticojejunostomy for drainage of the right posterior hepatic duct enabled total liver drainage
Authors: Kotaro Takeshita, Susumu Hijioka, Yuki Kawasaki, Yuta Maruki, Yoshikuni Nagashio, Takuji Okusaka, Yutaka Saito
Journal: Endoscopy (2023)

In a patient with unresectable malignant hilar biliary obstruction (MHBO), drainage of as much liver volume as possible is recommended [1] [2]. However, the retrograde approach is difficult owing to anatomic factors or the extent of stenosis, particularly in the right posterior hepatic duct. We report a case in which endoscopic ultrasound-guided hepaticojejunostomy (EUS-HJS) of the right posterior hepatic duct allowed total liver drainage ([Video 1]).
PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection
Authors: Eliano P. Navarese, Przemysław Podhajski, Paul A. Gurbel, Klaudyna Grzelakowska, Eleonora Ruscio, Udaya Tantry, Przemysław Magielski, Aldona Kubica, Piotr Niezgoda, Piotr Adamski, Roman Junik, Grzegorz Przybylski, Marta Pilaczyńska-Cemel, Manali Rupji, Giuseppe Specchia, Jarosław Pinkas, Robert Gajda, Diana A. Gorog, Felicita Andreotti, Jacek Kubica
Journal: Journal of the American College of Cardiology (2023)
Albuminuria and Heart Failure
Authors: Muhammad Shahzeb Khan, Izza Shahid, Stefan D. Anker, Gregg C. Fonarow, Marat Fudim, Michael E. Hall, Adrian Hernandez, Alanna A. Morris, Tariq Shafi, Matthew R. Weir, Faiez Zannad, George L. Bakris, Javed Butler
Journal: Journal of the American College of Cardiology (2023)
Declining Incidence of Postoperative Neonatal Brain Injury in Congenital Heart Disease
Authors: Shabnam Peyvandi, Duan Xu, A. James Barkovich, Dawn Gano, Vann Chau, V. Mohan Reddy, Thiviya Selvanathan, Ting Guo, J. William Gaynor, Mike Seed, Steven P. Miller, Patrick McQuillen
Journal: Journal of the American College of Cardiology (2023)
Features of tumor-microenvironment images predict targeted therapy survival benefit in patients with EGFR-mutant lung cancer
Authors: Shidan Wang, Ruichen Rong, Donghan M. Yang, Junya Fujimoto, Justin A. Bishop, Shirley Yan, Ling Cai, Carmen Behrens, Lynne D. Berry, Clare Wilhelm, Dara Aisner, Lynette Sholl, Bruce E. Johnson, David J. Kwiatkowski, Ignacio I. Wistuba, Paul A. Bunn, John Minna, Guanghua Xiao, Mark G. Kris, Yang Xie
Journal: Journal of Clinical Investigation (2023)

Tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) are effective for many patients with lung cancer with EGFR mutations. However, not all patients are responsive to EGFR TKIs, including even those harboring EGFR-sensitizing mutations. In this study, we quantified the cells and cellular interaction features of the tumor microenvironment (TME) using routine H&E-stained biopsy sections. These TME features were used to develop a prediction model for survival benefit from EGFR TKI therapy in patients with lung adenocarcinoma and EGFR-sensitizing mutations in the Lung Cancer Mutation Consortium 1 (LCMC1) and validated in an independent LCMC2 cohort. In the validation data set, EGFR TKI treatment prolonged survival in the predicted-to-benefit group but not in the predicted-not-to-benefit group. Among patients treated with EGFR TKIs, the predicted-to-benefit group had prolonged survival outcomes compared with the predicted not-to-benefit group. The EGFR TKI survival benefit positively correlated with tumor-tumor interaction image features and negatively correlated with tumor-stroma interaction. Moreover, the tumor-stroma interaction was associated with higher activation of the hepatocyte growth factor/MET-mediated PI3K/AKT signaling pathway and epithelial-mesenchymal transition process, supporting the hypothesis of fibroblast-involved resistance to EGFR TKI treatment.
Accelerated resolution of inflammation underlies sex differences in inflammatory responses in humans
Authors: Krishnaraj S. Rathod, Vikas Kapil, Shanti Velmurugan, Rayomand S. Khambata, Umme Siddique, Saima Khan, Sven Van Eijl, Lorna C. Gee, Jascharanpreet Bansal, Kavi Pitrola, Christopher Shaw, Fulvio D’Acquisto, Romain A. Colas, Federica Marelli-Berg, Jesmond Dalli, Amrita Ahluwalia
Journal: Journal of Clinical Investigation (2023)
Lessons learned: from mentored to mentor
Authors: Joseph Heitman
Journal: Journal of Clinical Investigation (2023)

This Viewpoint was written in association with the 25th anniversary of the American Society for Clinical Investigation's (ASCI's) Stanley J. Korsmeyer Award, which honors the highest standards of scientific excellence, meritorious research, intellectual integrity, and the mentoring of future life-science researchers. In 2018, the award recognized Joseph Heitman (Figure 1), for his key contributions to our understanding of how eukaryotic microbial pathogens evolve, cause disease, and develop drug resistance and his discovery of TOR and FKBP12 as targets of the immunosuppressive chemotherapeutic drug rapamycin. Dr. Heitman has mentored numerous undergraduates, medical students, graduate students, and postdoctoral and medical fellows, many of whom have developed independent careers in medicine and basic biomedical research.
Targeting ryanodine receptors to treat human diseases
Authors: Andrew R. Marks
Journal: Journal of Clinical Investigation (2023)

This Review provides an update on ryanodine receptors (RyRs) and their role in human diseases of heart, muscle, and brain. Calcium (Ca2+) is a requisite second messenger in all living organisms. From C. elegans to mammals, Ca2+ is necessary for locomotion, bodily functions, and neural activity. However, too much of a good thing can be bad. Intracellular Ca2+ overload can result in loss of function and death. Intracellular Ca2+ release channels evolved to safely provide large, rapid Ca2+ signals without exposure to toxic extracellular Ca2+. RyRs are intracellular Ca2+ release channels present throughout the zoosphere. Over the past 35 years, our knowledge of RyRs has advanced to the level of atomic-resolution structures revealing their role in the mechanisms underlying the pathogenesis of human disorders of heart, muscle, and brain. Stress-induced RyR-mediated intracellular Ca2+ leak in the heart can promote heart failure and cardiac arrhythmias. In skeletal muscle, RyR1 leak contributes to muscle weakness in inherited myopathies, to age-related loss of muscle function and cancer-associated muscle weakness, and to impaired muscle function in muscular dystrophies, including Duchenne. In the brain, leaky RyR channels contribute to cognitive dysfunction in Alzheimer’s disease, posttraumatic stress disorder, and Huntington’s disease. Novel therapeutics targeting dysfunctional RyRs are showing promise.
The kynurenine pathway implicated in patient delirium: possible indications for indoleamine 2,3 dioxygenase inhibitors
Authors: Amy B. Heimberger, Rimas V. Lukas
Journal: Journal of Clinical Investigation (2023)

Tryptophan (Trp) metabolism plays a central role in sleep, mood, and immune system regulation. The kynurenine pathway (KP), which is regulated by the enzymes tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3 dioxygenase (IDO), which catalyze the conversion of Trp to kynurenine (Kyn), facilitates immune regulation and influences neurocognition. Notably, Kyn metabolites bind the N-methyl-d-aspartate receptor (NMDAR), essential for memory encoding, and in turn, cognition. Aberrant NMDAR activity through agonist binding influences excitability and cell death. In this issue of the JCI, Watne and authors demonstrate that KP pathway end products were elevated in the serum and the cerebrospinal fluid (CSF) of subjects with delirium. This observation provides insight regarding the basis of a variety of commonly observed clinical conditions including sundowning, abnormal sleep-wake cycles in hospitalized patients, neurodegenerative cognitive impairment, radiation-induced cognitive impairment, neurocognitive symptomatology related to COVID-19, and clinical outcomes observed in patients with CNS tumors, such as gliomas.
Reprogramming dysfunctional CD8+ T cells to promote properties associated with natural HIV control
Authors: Federico Perdomo-Celis, Caroline Passaes, Valérie Monceaux, Stevenn Volant, Faroudy Boufassa, Pierre de Truchis, Morgane Marcou, Katia Bourdic, Laurence Weiss, Corinne Jung, Christine Bourgeois, Cécile Goujard, Laurence Meyer, Michaela Müller-Trutwin, Olivier Lambotte, Asier Sáez-Cirión
Journal: Journal of Clinical Investigation (2023)

In Figure 1E, the data for BCL-6 was inadvertently omitted, with a duplicate of the data for TOX shown on that line instead.
Entry receptors — the gateway to alphavirus infection
Authors: Ofer Zimmerman, Autumn C. Holmes, Natasha M. Kafai, Lucas J. Adams, Michael S. Diamond
Journal: Journal of Clinical Investigation (2023)

Alphaviruses are enveloped, insect-transmitted, positive-sense RNA viruses that infect humans and other animals and cause a range of clinical manifestations, including arthritis, musculoskeletal disease, meningitis, encephalitis, and death. Over the past four years, aided by CRISPR/Cas9-based genetic screening approaches, intensive research efforts have focused on identifying entry receptors for alphaviruses to better understand the basis for cellular and species tropism. Herein, we review approaches to alphavirus receptor identification and how these were used for discovery. The identification of new receptors advances our understanding of viral pathogenesis, tropism, and evolution and is expected to contribute to the development of novel strategies for prevention and treatment of alphavirus infection.
Immune checkpoint blockade in glioblastoma: from tumor heterogeneity to personalized treatment
Authors: Víctor A. Arrieta, Crismita Dmello, Daniel J. McGrail, Daniel J. Brat, Catalina Lee-Chang, Amy B. Heimberger, Dhan Chand, Roger Stupp, Adam M. Sonabend
Journal: Journal of Clinical Investigation (2023)

Immune checkpoint blockade (ICB) has revolutionized modern cancer therapy, arousing great interest in the neuro-oncology community. While several reports show that subsets of patients with glioma exhibit durable responses to immunotherapy, the efficacy of this treatment has not been observed for unselected patient populations, preventing its broad clinical implementation for gliomas and glioblastoma (GBM). To exploit the maximum therapeutic potential of ICB for patients with glioma, understanding the different aspects of glioma-related tumor immune responses is of critical importance. In this Review, we discuss contributing factors that distinguish subsets of patients with glioma who may benefit from ICB. Specifically, we discuss (a) the complex interaction between the tumor immune microenvironment and glioma cells as a potential influence on immunotherapy responses; (b) promising biomarkers for responses to immune checkpoint inhibitors; and (c) the potential contributions of peripheral immune cells to therapeutic responses.
BMX controls 3βHSD1 and sex steroid biosynthesis in cancer
Authors: Xiuxiu Li, Michael Berk, Christopher Goins, Mohammad Alyamani, Yoon-Mi Chung, Chenyao Wang, Monaben Patel, Nityam Rathi, Ziqi Zhu, Belinda Willard, Shaun Stauffer, Eric Klein, Nima Sharifi
Journal: Journal of Clinical Investigation (2023)

Prostate cancer is highly dependent on androgens and the androgen receptor (AR). Hormonal therapies inhibit gonadal testosterone production, block extragonadal androgen biosynthesis, or directly antagonize AR. Resistance to medical castration occurs as castration-resistant prostate cancer (CRPC) and is driven by reactivation of the androgen-AR axis. 3β-hydroxysteroid dehydrogenase-1 (3βHSD1) serves as the rate-limiting step for potent androgen synthesis from extragonadal precursors, thereby stimulating CRPC. Genetic evidence in men demonstrates the role of 3βHSD1 in driving CRPC. In postmenopausal women, 3βHSD1 is required for synthesis of aromatase substrates and plays an essential role in breast cancer. Therefore, 3βHSD1 lies at a critical junction for the synthesis of androgens and estrogens, and this metabolic flux is regulated through germline-inherited mechanisms. We show that phosphorylation of tyrosine 344 (Y344) occurs and is required for 3βHSD1 cellular activity and generation of Δ4, 3-keto-substrates of 5α-reductase and aromatase, including in patient tissues. BMX directly interacts with 3βHSD1 and is necessary for enzyme phosphorylation and androgen biosynthesis. In vivo blockade of 3βHSD1 Y344 phosphorylation inhibits CRPC. These findings identify what we believe to be new hormonal therapy pharmacologic vulnerabilities for sex-steroid dependent cancers.
A phosphorylation switch controls androgen biosynthesis in prostate cancer
Authors: Yun Qiu
Journal: Journal of Clinical Investigation (2023)

Androgen biosynthesis enzyme 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1) encoded by HSD3B1 has emerged as a potential driver for therapeutic resistance in prostate cancer. Patients with homozygous HSD3B1(1245C) inheritance are intrinsically more resistant to currently available androgen/androgen receptor-targeting (AR-targeting) drugs. In this issue of the JCI, Li et al. present data on the regulation of 3βHSD1 phosphorylation and activity by tyrosine kinase BMX. Inhibition of BMX activity by genetic or pharmacologic approaches blocked androgen biosynthesis in prostate cancer cells and inhibited tumor growth in preclinical xenograft models. The findings provide insights into mechanisms underlying castration resistance in prostate cancer and reveal a potential strategy to circumvent therapeutic resistance in patients with homozygous HSD3B1(1245C) inheritance.
Beyond adaptive immunity: induction of trained immunity by COVID-19 adenoviral vaccines
Authors: Mihai G. Netea, Leo A.B. Joosten
Journal: Journal of Clinical Investigation (2023)

The COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, has resulted in much human suffering and societal disruption. The ChAdOx1 nCoV-19 vaccine against COVID-19 has had a crucial role in the fight against the pandemic. While ChAdOx1 nCoV-19 has been shown to induce adaptive B and T cell responses, which protect against COVID-19, in this issue of the JCI, Murphy et al. show that this vaccine also induces trained innate immunity. This finding contributes to a better understanding of the complex immunological effects of adenoviral-based vaccines, provides the possibility of clinically relevant heterologous effects of these vaccines, and suggests that other adenoviral-based vaccines may induce trained immunity.